Chaperone-like antibodies targeting misfolded tau protein: new vistas in the immunotherapy of neurodegenerative foldopathies.
Neurodegenerative foldopathies are characterized by aberrant folding of proteins leading to the intracellular and extracellular accumulation of insoluble misfolded proteins. One of the most prominent protein folding disorders is Alzheimer's disease (AD). In AD, there were identified two major driving forces behind neurodegeneration, misfolded proteins tau and amyloid-beta. Tau belongs to a family of intrinsically disordered proteins that are characterized by the absence of a rigid three-dimensional structure in their natural environment. However, in disease condition, tau truncation and hyperphosphorylation could lead to tau transformation from intrinsically disordered protein into highly ordered soluble and insoluble misfolded structures. Increased understanding of the molecular mechanism underlying pathological transformation of tau protein has opened up the possibility of targeting misfolded tau for therapeutic purposes. Pharmacological research has identified several therapeutic approaches targeting directly or indirectly tau cascade. Novel promising field of AD treatment represent monoclonal antibodies with chaperon like activities that will be able to neutralize the toxic gain of function of misfolded tau and thus increase its degradation. We suggest that chaperon like antibodies targeting disease modified tau may hold promise for the successful treatment of AD and related foldopathies.
Zilka
Norbert
N
Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Bratislava, Slovak Republic.
Kontsekova
Eva
E
Novak
Michal
M
D000544:Alzheimer Disease / Q000628:therapy; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D018832:Molecular Chaperones / Q000276:immunology*; D019636:Neurodegenerative Diseases / Q000628:therapy*; D017510:Protein Folding; D016875:tau Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D018832:Molecular Chaperones; D016875:tau Proteins